Work is continuing on the conformational changes which occur in the protein serum albumin as a function of pH and other variables. The neutral transition and its relationship to calcium binding is being investigated. Particular emphasis is being placed on the action of proteolytic enzymes which occur in plasma and are also found associated with albumin. These enzymes cleave the albumin molecule in a relatively restricted fashion when the conformation is non-native, but the native form appears to be quite resistant. Thus the enzymatic susceptibility provides another measure of conformational alteration, and studies are being conducted as a function of pH, temperature, urea concentration, etc. It is anticipated that these studies will also exhibit a relationship between susceptibility to enzymatic cleavage and the microheterogeneity known to exist in this protein. Thus it is expected that under a given set of conditions, some of the albumin molecules will exist in a resistant (native) conformation while others will be found to be susceptible to degradation. It is anticipated that these studies will throw considerable light on the physiological role of plasma albumin and on the mechanism of its turn-over in the bloodstream.